Aim: 

Despite a well-described pathological phenotype, the molecular pathways leading to nigrostriatal neuron degeneration in Parkinson's disease (PD) remain to be fully understood. A role for metalloproteinases (MMPs) and plasminogen activator (PA)/plasmin systems in neurodegenerative diseases has been proposed. However, their involvement in PD pathogenesis is still seldom, or none, explored. We, therefore, investigated changes in mRNA and protein levels of MMP-9 and of components of the PA/plasmin system: plasminogen, tissue-type PA (tPA), annexin II and LRP (tPA-plasminogen receptors), in the substantia nigra pars compacta (SNpc) of 1-methyl-4-phenyl-1,2,3,6-tetrahydropiridine (MPTP)-injected mice, an animal model of PD.

Methods: 

C57/Bl6 mice received acute administration of MPTP (80 mg/Kg) and were killed 1, 24, 48 and 72 h, 1 and 2 wk after last MPTP injection. Control animals received saline administration. Real-time RT-PCR and/or Western immunoblot were used to investigate changes in mRNA and protein levels of the above mentioned proteins.

Results: 

MMP-9 mRNA level decreased significantly, compared with control, 1 h after MPTP injection, increased at 24 h and remained higher than control in the following dates. Protein levels of both pro- and active MMP-9 increased significantly at 24 h, similarly to mRNA, decreased near control level by 72 h and further increased at 1–2 wk. mRNA levels of PA/plasmin system components changed in accord to one another: all mRNAs increased at 1 h (being significant only for annexin II and LRP) and then decreased to control levels, or significantly lower, at 24–48 h.

Conclusion: 

Our results suggest an involvement of MMP-9 in two events characterizing MPTP-induced parkinsonism: early SNpc neuronal degeneration (24–48 h), which associates with an inflammatory response, and late axonal regeneration of survived neurons. From mRNA data we can speculate that also the PA/plasmin system may be involved in the first event, although data on corresponding protein levels are needed.